Study detailed in Cancer Research describes threshold for Myc in immune system cancer.

Scientists at the Stanford University School of Medicine report that lowering levels of a cancer signal beyond a specific point in mice reverses uncontrolled cell growth, returning tumor cells to their normal state.

The researchers identified a precise threshold of the signaling molecule Myc that determined the fate of tumor cells in an immune system cancer. Above the threshold, Myc drove immune cells to grow too large and multiply uncontrollably. When Myc levels were lowered, the same cells shrank to normal size, stopped multiplying, and began dying normally, according to the Stanford team.

Previous research demonstrated that turning Myc and other cancer signals all the way off can kill a tumor. This is the first time, however, that scientists have demonstrated a specific point at which a cancer signal reverted to a healthy level, remarks Catherine Shachaf, Ph.D., an instructor in microbiology and immunology and lead coauthor of the study.

This is an important finding, since Myc functions in both healthy and cancerous cells as a transcription factor. Myc is essential at lower levels for normal cell function. So switching Myc all the way off is not an option for treating cancer, the investigators point out.

The Stanford group used mice that were genetically engineered to develop Myc-driven tumors in response to a chemical in their drinking water. They lowered Myc from the cancer-causing level to the point at which tumor cells returned to normal. At this level the researchers examined changes in gene activity, protein levels, protein activation inside the cells, and the appearance of cell-labeling proteins on the exterior surface of the cells. They then created a program to help them see how these different types of data fit together.

“At the Myc threshold, there is a big change: Programmed cell death becomes dominant over growth,” explains Andrew Gentles, Ph.D., a research associate in radiology, and lead coauthor of the paper. The threshold was characterized by both a return of normal controls on the cell’s life cycle, which stopped inappropriate growth, and reactivation of the pathways that prompt normal cell death, he continues.

The findings are published in the July 1 issue of Cancer Research.

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